Recent structural and mechanistic insights into endplate acetylcholine receptors

Steven M. Sine, Fan Gao, Won Yong Lee, Nuriya Mukhtasimova, Hai Long Wang, Andrew G. Engel

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

Voluntary movement mediated by skeletal muscle relies on endplate acetylcholine receptors (AChR) to detect nerve-released ACh and depolarize the muscle fiber. Recent structural and mechanistic studies of the endplate AChR have catalyzed a leap in our understanding of the molecular steps in this chemical-to-electrical transduction process. Studies of acetylcholine binding protein (AChBP) give insight into ACh recognition, the first step in activation of the AChR. An atomic structural model of the Torpedo AChR at a resolution of 0.4 nm, together with single-ion channel recording methods, allow tracing of the link between the agonist binding event and gating of the ion channel, as well as determination of how the channel moves when it opens to allow flow of cations. Structural models of the human AChR enable precise mapping of disease-causing mutations, while studies of the speed with which single AChR channels open and close cast light on pathogenic mechanisms.

Original languageEnglish (US)
Title of host publicationMyasthenia Gravis and Related Disorders 11th International Conference
PublisherBlackwell Publishing Inc.
Pages53-60
Number of pages8
ISBN (Print)9781573316873
DOIs
StatePublished - Jun 2008

Publication series

NameAnnals of the New York Academy of Sciences
Volume1132
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Acetylcholine binding protein
  • Acetylcholine receptor
  • Agonist recognition
  • Binding-gating coupling mechanism
  • Congenital myasthenic syndrome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Sine, S. M., Gao, F., Lee, W. Y., Mukhtasimova, N., Wang, H. L., & Engel, A. G. (2008). Recent structural and mechanistic insights into endplate acetylcholine receptors. In Myasthenia Gravis and Related Disorders 11th International Conference (pp. 53-60). (Annals of the New York Academy of Sciences; Vol. 1132). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1405.041